Acid Α-linolenic Acid Research Articles

Effects of a rapeseed oil-enriched hypoenergetic diet with a high content of α-linolenic acid on body weight and cardiovascular risk profile in patients with the metabolic syndrome

In therapy of the metabolic syndrome, the optimal dietary approach with regard to its macronutrient composition and metabolically favourable food components, such as the plant-derived n-3 fatty acid α-linolenic acid (ALA), is still a matter of debate. We investigated the effects of a hypoenergetic diet with low energy density (ED) enriched in rapeseed oil, resulting in high MUFA content and an ALA intake of 3.5 g/d on body weight and cardiovascular risk profile in eighty-one patients with the metabolic syndrome in comparison with an olive oil diet rich in MUFA, but with a low ALA content. After a 6-month dietary intervention, body weight was significantly reduced in the rapeseed oil and olive oil groups ( -7.8 v. -6.0 kg; P < 0.05). There were significant decreases in systolic blood pressure, total cholesterol and LDL-cholesterol, and insulin levels in both groups (P < 0.05). For all of these changes, no inter-group differences were observed. After the rapeseed oil diet, diastolic blood pressure declined more than after the olive oil diet (P < 0.05 for time × group interaction). Furthermore, concentrations of serum TAG were significantly reduced after the high ALA intake, but not in the low ALA group (P < 0.05 for time × group interaction). In conclusion, our dietary food pattern with a low ED and high intakes of MUFA and ALA may be a practical approach for long-term dietary treatment in patients with the metabolic syndrome, leading to weight reduction and an improvement in the overall cardiovascular risk profile.

Circulating and dietary α-linolenic acid and incidence of congestive heart failure in older adults: the Cardiovascular Health Study

Few studies have evaluated the association between the n-3 fatty acid α-linolenic acid (ALA) and the incidence of congestive heart failure (CHF). We investigated whether plasma phospholipid concentrations and estimated dietary consumption of ALA are associated with incident CHF. We used data from the Cardiovascular Health Study, a prospective cohort study of cardiovascular diseases among adults aged ≥65 y, from 4 US communities. A total of 2957 participants free of prevalent heart disease and with available fatty acid measurements were included in biomarker analyses (30,722 person-years and 686 incident CHF events). A total of 4432 participants free of prevalent heart disease were included in dietary analyses (52,609 person-years and 1072 events). We investigated the association of ALA with incident CHF by using Cox regression. After adjustment for age, sex, race, education, smoking status, BMI, waist circumference, and alcohol consumption, plasma phospholipid ALA was not associated with incident CHF (HR for the highest compared with the lowest quartile: 0.97; 95% CI: 0.79, 1.21; P-trend = 0.85). Likewise, dietary ALA was not associated with incident CHF (adjusted HR for the highest compared with the lowest quartile: 0.96; 95% CI: 0.82, 1.20; P-trend = 0.97). We observed no association of biomarker or dietary ALA with nonvalvular CHF subtype. We also found little evidence of an association between ALA and CHF in subgroups based on age, sex, diabetes, fish consumption, BMI, or FADS2 genotype (rs1535). ALA intake is not associated with incident CHF in older adults. This trial was registered at clinicaltrials.gov as NCT00005133.

Dietary flaxseed oil reduces adipocyte size, adipose monocyte chemoattractant protein-1 levels and T-cell infiltration in obese, insulin-resistant rats

BackgroundAdipocyte dysfunction is characterized by an increase in adipocyte size and changes to their adipokine profiles. Immune cell infiltration into adipose tissue is thought to contribute to the metabolic complications of obesity, with local and systemic consequences for the inflammatory status of the obese individual. Dietary interventions with omega-3 fatty acids from marine sources have been successful at reducing inflammation. The aim of this study was to determine whether flaxseed oil containing the plant-based omega-3 fatty acid α-linolenic acid (ALA) is an effective modulator of inflammation and adipocyte dysfunction. MethodsSeventeen-week old male fa/fa and lean Zucker rats were fed a control diet (faCTL, lnCTL) and fa/fa rats were fed an ALA-rich flaxseed oil supplemented diet (faFLAX) for 8weeks. Adipose tissue and serum were collected and analyzed for cytokine (IL-6, IL-10, IL-18, IL-2, IFN-γ, TNF-α), haptoglobin, monocyte chemoattractant protein-1 (MCP-1) and adipokine (leptin, adiponectin) levels. Splenocytes were isolated and ex vivo mitogen-stimulated cytokine production was measured. Digital images of adipose tissue sections were used to quantify adipocyte area. Macrophage and T-cell infiltration were assessed in adipose tissue by immunohistochemistry. ResultsfaFLAX rats had 17% smaller adipocytes and 5-fold lower MCP-1 levels in adipose tissue than faCTL rats. Adipose tissue levels of IL-10 were 72% lower in the faFLAX group compared to baseline, and TNF-α levels decreased 80% (equal to lnCTL levels) in the faFLAX group compared to faCTL. There were no changes in ex vivo cytokine production by splenocytes between faFLAX and faCTL. Macrophage infiltration was not different among groups; however, faFLAX rats had less T-cell infiltration than faCTL rats. ConclusionsDietary intervention with ALA-rich flaxseed oil in obese Zucker rats reduced adipocyte hypertrophy, protein levels of inflammatory markers MCP-1 and TNF-α, and T-cell infiltration in adipose tissue. Modest improvements to other parameters of obesity were also observed. The results suggest that, due to its ability to improve adipocyte function, ALA-rich flaxseed oil confers health benefits in obesity.

Different dietary omega-3 sources during pregnancy and DHA in the developing rat brain

The essential n-3 fatty acid α-linolenic acid (ALA) can be converted into eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA) and docosahexaenoic acid (DHA) under the action of desaturase and elongase enzymes. Human studies have demonstrated that females convert a higher proportion of ALA into EPA and DHA than males. We have demonstrated that when fed upon an ALA rich diet, female rats have a significantly higher EPA content of plasma and liver lipids than males. When fetal tissues were collected, it was observed that pups from dams fed the ALA rich diet had a comparable brain DHA status to those from dams fed on a salmon-oil based diet, indicating that conversion of ALA to DHA during pregnancy was efficient, and that DHA accumulated in a tissue-specific manner. Similar efficacy of dietary ALA in women during pregnancy would mean that plant n-3 fatty acids would be useful alternatives to preformed EPA and DHA.

Dietary Intakes of Arachidonic Acid and α-Linolenic Acid Are Associated with Reduced Risk of Hip Fracture in Older Adults

PUFA are hypothesized to influence bone health, but longitudinal studies on hip fracture risk are lacking. We examined associations between intakes of PUFA and fish, and hip fracture risk among older adults (n = 904) in the Framingham Osteoporosis Study. Participants (mean age ~75 y at baseline) were followed for incident hip fracture from the time they completed the baseline exam (1988–1989) until December 31, 2005. HR and 95% CI were estimated for energy-adjusted dietary fatty acid exposure variables [(n-3) fatty acids: α-linolenic acid (ALA), EPA, DHA, EPA+DHA; (n-6) fatty acids: linoleic acid, arachidonic acid (AA); and the (n-6):(n-3) ratio] and fish intake categories, adjusting for potential confounders and covariates. Protective associations were observed between intakes of ALA (P-trend = 0.02) and hip fracture risk in a combined sample of women and men and between intakes of AA (P-trend = 0.05) and hip fracture risk in men only. Participants in the highest quartile of ALA intake had a 54% lower risk of hip fracture than those in the lowest quartile (Q4 vs. Q1: HR = 0.46; 95% CI = 0.26–0.83). Men in the highest quartile of AA intake had an 80% lower risk of hip fracture than those in the lowest quartile (Q4 vs. Q1: HR = 0.20; 95% CI = 0.04–0.96). No significant associations were observed among intakes of EPA, DHA, EPA+DHA, or fish. These findings suggest dietary ALA may reduce hip fracture risk in women and men and dietary AA may reduce hip fracture risk in men.

Lipid redistribution by α-linolenic acid-rich chia seed inhibits stearoyl-CoA desaturase-1 and induces cardiac and hepatic protection in diet-induced obese rats

Chia seeds contain the essential fatty acid, α-linolenic acid (ALA). This study has assessed whether chia seeds attenuated the metabolic, cardiovascular and hepatic signs of a high-carbohydrate, high-fat (H) diet [carbohydrates, 52% (wt/wt); fat, 24% (wt/wt) with 25% (wt/vol) fructose in drinking water] in rats. Diets of the treatment groups were supplemented with 5% chia seeds after 8 weeks on H diet for a further 8 weeks. Compared with the H rats, chia seed-supplemented rats had improved insulin sensitivity and glucose tolerance, reduced visceral adiposity, decreased hepatic steatosis and reduced cardiac and hepatic inflammation and fibrosis without changes in plasma lipids or blood pressure. Chia seeds induced lipid redistribution with lipid trafficking away from the visceral fat and liver with an increased accumulation in the heart. The stearoyl-CoA desaturase-1 products were depleted in the heart, liver and the adipose tissue of chia seed-supplemented rats together with an increase in the substrate concentrations. The C18:1 trans-7 was preferentially stored in the adipose tissue; the relatively inert C18:1n-9 was stored in sensitive organs such as liver and heart and C18:2n-6, the parent fatty acid of the n-6 pathway, was preferentially metabolized. Thus, chia seeds as a source of ALA induce lipid redistribution associated with cardioprotection and hepatoprotection.

Agonism with the omega-3 fatty acids α-linolenic acid and docosahexaenoic acid mediates phosphorylation of both the short and long isoforms of the human GPR120 receptor

The newly discovered G protein-coupled receptor GPR120 has recently been shown to stimulate secretion of the gut hormones glucagon-like peptide-1 and cholecystokinin upon binding of free fatty acids, thrusting it to the forefront of drug discovery efforts for treatment of type 2 diabetes as well as satiety and obesity. Although sequences for two alternative splice variants of the human GPR120 receptor have been reported, there have been no studies which directly compare the signaling of these isoforms. We have identified an additional 16 amino acid gap containing four phospho-labile serine/threonine residues which is localized to the third intracellular loop of the GPR120-long (GPR120-L) isoform. Based on this finding, we hypothesized that the agonist-stimulated phosphorylation profiles of this isoform would be distinct from that of the short isoform (GPR120-S). Using a clonal HEK293 cell model, we examined agonist-mediated phosphorylation of GPR120-S and GPR120-L with the omega-3 fatty acids α-linolenic acid (ALA) and docosahexaenoic acid (DHA). Our results show rapid phosphorylation of both isoforms following agonism by either ALA or DHA. Moreover, we show no significant difference in the degree or rate of phosphorylation of both isoforms upon agonism with either ALA or DHA, suggesting that the additional gap in the longer variant is not phosphorylated. Importantly, our results demonstrate that the shorter variant exhibits significantly more pronounced basal phosphorylation in the absence of agonist, suggesting that the additional gap in the long variant may contribute to masking of constitutive phosphorylation sites. These are the first results which demonstrate specific phosphorylation of GPR120 isoforms upon agonism by free fatty acids and the first which distinguish the phosphorylation profiles of the two GPR120 isoforms.

Omega‐3 fatty acid mediated phosphorylation of the short and long human GPR120 receptor isoforms

The orphan G protein‐coupled receptor, GPR120, has recently been thrust to the forefront of diabetes research due to its ability to stimulate release of the insulin secretagogue glucagon‐like peptide 1. While the molecular aspects involved in GPR120 signaling remain elusive, it has been shown that long chained free fatty acids, including the omega‐3 fatty acids α‐linolenic acid (ALA) and docosahexaenoic acid (DHA), are agonists of GPR120. We have recently cloned the human and rat GPR120 genes and have discovered that the human receptor can be alternatively spliced, yielding distinct short and long isoforms. Interestingly, we have identified that GPR120‐long contains an additional 16 amino acids within the third intracellular loop, and importantly, this region contains four phospho‐labile residues. Based on this distinct difference, we hypothesized that the long and short GPR120 isoforms have differing phosphorylation and desensitization profiles. Here, we present data which compares the phosphorylation of both variants upon agonism with various omega‐3 fatty acids. We also present data regarding the molecular mechanisms of GPR120 phosphorylation. Our data, taken together with the variation of the sequences encoding the third intracellular loop, suggest that the two GPR120 isoforms have distinct desensitization profiles. This project is funded by the Diabetes Action Research and Education Foundation.

Effect of dietary fatty acid intake on prospective weight change in the Heidelberg cohort of the European Prospective Investigation into Cancer and Nutrition

To evaluate the association between fatty acid (alpha-linolenic acid (ALA), EPA, DHA, palmitic, stearic, oleic, linoleic and arachidonic acids) intake and prospective weight change in the Heidelberg cohort of the European Prospective Investigation into Cancer and Nutrition. Prospective cohort study with mean follow-up time of 6.5 years. In a total of 9182 men and 10867 women aged 35 to 64 years, from body weight measurement at recruitment and calibrated body weight during follow-up, weight change was expressed as mean annual weight change relative to baseline weight (%/year) and categorised into four groups (weight loss, <-2.5%/5 years; stable weight, between -2.5 and +2.5%/5 years; small weight gain, > or =2.5 to <7.5%/5 years; large weight gain, > or =7.5%/5 years). Energy-adjusted dietary fatty acid intake data were estimated from the FFQ completed at baseline. Multivariate linear regression models as well as multinomial logistic regression analyses (carbohydrate replacement models) were conducted. Stearic acid intake was linearly associated with weight gain (P < 0.01) in men and women. Linear associations also existed for ALA and arachidonic acid intake, significantly so in women. In multinomial models, women in the highest tertile of ALA and stearic acid intake showed increased OR (95 % CI) for small weight gain (1.16 (0.94, 1.88) and 1.24 (1.08, 1.43), respectively), and large weight gain (1.39 (1.03, 1.88) and 1.56 (1.27, 1.90), respectively), whereas OR were non-significantly increased in men. Dietary intake of ALA was inversely associated with large (0.80 (0.65, 0.99)) weight gain in women only. These results suggest differential effects of single dietary fatty acids on prospective weight gain in adults.

Distribution of omega-3 fatty acids in tissues of rabbits fed a flaxseed-supplemented diet

Diets rich in omega-3 polyunsaturated fatty acids are associated with decreased incidences of cardiovascular disease. The extent of incorporation and distribution of these beneficial fats into body tissues is uncertain. Rabbits were fed regular rabbit chow or a diet containing 10% ground flaxseed that is highly enriched with the omega-3 polyunsaturated fatty acid α-linolenic acid (ALA). The high-flaxseed diet resulted in an incorporation of ALA in all tissues, but mostly in the heart and liver with little in the brain. Docosahexaenoic and eicosapentaenoic acid levels were also selectively increased in some tissues, and the effects were not as large as ALA. Arachidonic acid and the ratio of ω-6/ ω-3 fatty acids were decreased in all tissues obtained from the flax-supplemented group. Consumption of dietary flaxseed appears to be an effective means to increase ALA content in body tissues, but the degree will depend upon the tissues examined.

Experimental and clinical research findings on the cardiovascular benefits of consuming flaxseed

Functional foods and nutraceuticals are becoming popular alternatives to pharmacological treatments by providing health benefits and (or) reducing the risk of chronic diseases. Flaxseed is a rich source of 3 components with demonstrated cardioprotective effects: the omega-3 fatty acid alpha-linolenic acid (ALA), dietary fibre, and phytoestrogen lignans. Multiple clinical dietary intervention trials report that consuming flaxseed daily can modestly reduce circulating total cholesterol (TC) by 6%-11% and low-density lipoprotein (LDL) cholesterol by 9%-18% in normolipemic humans and by 5%-17% for TC and 4%-10% for LDL cholesterol in hypercholesterolemic patients, as well as lower various markers associated with atherosclerotic cardiovascular disease in humans. Evidence to date suggests that the dietary fibre and (or) lignan content of flaxseed provides the hypocholesterolemic action. The omega-3 ALA found in the flaxseed oil fraction also contributes to the antiatherogenic effects of flaxseed via anti-inflammatory and antiproliferative mechanisms. Dietary flaxseed may also protect against ischemic heart disease by improving vascular relaxation responses and by inhibiting the incidence of ventricular fibrillation.

Relationship of omega-3 and omega-6 fatty acids with semen characteristics, and anti-oxidant status of seminal plasma: A comparison between fertile and infertile men

Fatty acid (FA) composition of the spermatozoa may be an important determinant of fertility. The aim was to evaluate polyunsaturated fatty acid (PUFA) composition of the blood plasma and spermatozoa in infertile men with idiopathic oligoasthenoteratozoospermia (OAT). Eighty-two infertile men with idiopathic OAT and seventy-eight fertile men defined according to semen concentration and proven fertility were enrolled in the study. The semen parameters were assessed according to World Health Organization criteria; three omega-3 fatty acids--alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and two omega-6 fatty acids--linoleic acid (LA) and arachidonic acid (AA) concentrations were measured in blood plasma and spermatozoa; and the seminal plasma enzymatic antioxidant levels of catalase, and superoxide dismutase (SOD) were also assessed. Proven fertile men had higher blood and spermatozoa levels of omega-3 FAs compared with the infertile patients. The ratio of serum omega-6/omega-3 fatty acids was significantly higher in infertile (14.8+/-4.3) patients compared to fertile controls (6.3+/-2.2) (P=0.001). Additionally, levels of AA were higher and the omega-3 index (EPA+DHA) was lower in infertile subjects than in fertile controls (all P values<0.05). Infertile men had higher mean AA:DHA ratio and AA:EPA (6.4+/-2.9 and 12.0+/-4.9, respectively) than fertile men (3.3+/-1.8 and 6.7+/-2.6, respectively) (both P=0.001). A strong negative correlation was found between the AA:DHA and AA:EPA ratios and total sperm count (r=-0.62, P=0.001 and r=-0.64, P=0.001, respectively), sperm motility (r=-0.63, P=0.001 and r=-0.61, P=0.001, respectively), and sperm morphology (r=-0.61, P=0.001, and r=-0.59, P=0.002, respectively). Infertile men had lower concentrations of omega-3 FAs in spermatozoa than fertile men. These results suggest that research should be performed to assess the potential benefits of omega-3 FA supplementation as a therapeutic approach in infertile men with idiopathic OAT.

Effect of long chain fatty acids on Salmonella killing, superoxide and nitric oxide production by chicken macrophages

The objective of this study was to investigate the effect of uptake of different commonly consumed long chain fatty acids on superoxide (O 2 −), nitric oxide (NO) production, and ability to kill Salmonella enterica serotype typhimurium ( S. typhimurium) by chicken macrophages (HD11 cells). All the fatty acids were taken up by HD11 cells with stearic acid uptake higher than polyunsaturated fatty acids. Uptake of green fluorescent protein-labeled bacteria and the viability of HD11 cells (measured by flow cytometry) was not affected by any of the fatty acids tested. Bacterial clearance (measured by the plating of sorted viable infected cells) was significantly higher with n − 3 fatty acids α-linolenic acid (ALA) and docosahexanoic acid (DHA). However, stearic acid (SA) and the n − 6 fatty acid, arachidonic acid (ARA) did not influence S. typhimurium killing by HD11 cells. The improved S. typhimurium clearance by ALA and DHA was not associated with increased NO or O 2 − production by HD11 cells. These results suggest a role for n − 3 polyunsaturated fatty acids in Salmonella clearance by chicken macrophages however in vivo studies are essential to confirm their efficacy in controlling Salmonella infection in chickens and contamination in shell eggs.

Gender differences in then-3 fatty acid content of tissues

Dietary n-3 PUFA have many beneficial effects on cell and tissue function and on human health. In mammals the n-3 essential fatty acid alpha-linolenic acid (ALNA) can be converted into longer-chain (LC) n-3 PUFA such as EPA and DHA via a series of desaturase and elongase enzymes that are mainly active in the liver. Human studies have identified that males and females appear to differ in their ability to synthesise EPA and DHA from ALNA, with associated differences in circulating concentrations. Based on studies of women using the contraceptive pill or hormone-replacement therapy and of trans-sexual subjects it is suggested that sex hormones play a role in these differences. The rat has been used to investigate gender differences in n-3 PUFA status since this model allows greater dietary control than is possible in human subjects. Like human subjects, female rats have higher plasma DHA concentrations than males. Rats also respond to increased dietary ALNA in a way that is comparable with available human data. The concentrations of LC n-3 PUFA in rat plasma and tissues are positively associated with circulating concentrations of oestradiol and progesterone and negatively associated with circulating concentrations of testosterone. These findings suggest that sex hormones act to modify plasma and tissue n-3 PUFA content, possibly by altering the expression of desaturase and elongase enzymes in the liver, which is currently under investigation.

Inflammatory markers are not altered by an eight week dietary α-linolenic acid intervention in healthy abdominally obese adult males and females

Atherogenesis is thought to be mediated by local and/or systemic production of pro-inflammatory cytokines and omega-3 fatty acids have been implicated in reducing these inflammatory markers. The objective of this study was to determine the effect of an isocaloric diet supplemented with a plant-based dietary omega-3 fatty acid [α-linolenic acid (ALA)] on interleukin-6, C-reactive protein, serum amyloid A, and tumor necrosis factor-α. Subjects included healthy adult males and females (∼79% female, average age 38 years) with increased waist circumference (mean WC = 99 cm) and body mass index (mean BMI = 29.8 kg/m 2) who were free of chronic disease, not taking medications, and sedentary. Control subjects ( n = 24) did not to alter their habitual diet and the ALA group ( n = 27) followed an enriched ALA diet by using flaxseed oil capsules (increasing ALA to 5% of total energy intake) and lowered their dietary fat consumption by a commensurate amount. Fasting blood samples were obtained before and after the 8-week intervention. We found no significant changes in the inflammatory factors after this 8-week dietary intervention. This study suggests there are no beneficial effects of an 8-week ALA intervention on these inflammatory factors among young, healthy, overweight/obese subjects whose inflammatory factors are not significantly elevated.

Dietary supplementation of N-3 fatty acids and hydroperoxide levels in rat retinas

Docosahexaenoic acid (DHA) plays an important role in visual and neural development in mammals. In the present study, effect of dietary supplementation with n-3 fatty acids, primarily docosahexaenoic acid (DHA) with high purity, on the fatty acid composition of photoreceptor cells of young rats (fed from 4 weeks) was investigated. DHA in rod outer segment (ROS) membranes was significantly increased in the group of high DHA feeding (9.69% total energy). Other n-3 fatty acids (α-linolenic acid (ALA) and eicosapentaenoic acid (EPA)) included in the diets with DHA (0.95%∼5.63% total energy) also significantly increased the proportion of DHA compared with the linoleic acid diet groups. However, the proportions of arachidonic acid (ARA) and other long chain n-6 fatty acids (22:4n6 and 22:5n6) were suppressed in these n-3 fatty acids-fed groups. Phospholipid hydroperoxides in ROS membranes were determined using a highly sensitive analytical technique, chemiluminescence-high performance liquid chromatography (CL-HPLC). There was no increasing tendency in the hydroperoxide levels of ROS membranes containing high content of DHA, and phosphatidylethanolamine hydroperoxide (PEOOH) was much lower than phosphatidylcholine hydroperoxide (PCOOH) under normal light conditions, which implies that DHA supplementation does not much affect the peroxidizability of ROS membranes in vivo. But UV irradiation on separated ROS membranes accelerated the formation of phospholipid hydroperoxides in high DHA feeding rats, and PEOOH was produced more efficiently than PCOOH in vitro.

Comparison of the effects of two low fat diets with different α-linolenic:linoleic acid ratios on coagulation and fibrinolysis

Fish oils rich in eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have been demonstrated to alter coagulation and fibrinolysis variables. This study compared the effects of a traditional cholesterol-lowering diet and a similar diet, which had 50% of the linoleic acid (LA) replaced with the 18 carbon n-3 fatty acid, α-linolenic acid (ALA), on selected hemostatic variables. After a 2-week run-in diet with 39.5% total energy (en) from fat, 29 healthy male subjects consumed a 31.5% en fat diet with approximately 7% en from polyunsaturated fat and an ALA:LA ratio of either 1:1.2 (ALA-rich, n=15) or 1:21 (LA-rich, n=14) for 6 weeks. Blood was collected at the beginning, middle and end of test diets for analysis of Factor VIIc and VIIIc, fibrinogen, von Willebrand factor, activated protein C resistance (APC™ resistance), tissue plasminogen activator and plasminogen activator inhibitor type-1 activities and/or protein concentrations and platelet fatty acids. The ALA-rich diet tripled the percentage of platelet EPA, ( P<0.0005) but had little effect on coagulation and fibrinolysis. The APC™ ratio demonstrated increased anticoagulant activity on the ALA-rich diet ( P<0.001) only. Studies in patients with vascular pathologies are indicated to corroborate the current findings. Greater ratios of ALA:LA, achievable only with greater amounts of polyunsaturated fat, may be necessary to produce the effects demonstrated after feeding fish oils.

Physicochemical Perturbation of α-Linolenic Acid Related to Cell Proliferation

Abstract The influence of fatty acids, α-linolenic acid (ALA), and linoleic acid (LA), on lipid membrane dynamics and cell proliferation was investigated. Electron-spin resonance measurements with 2-hexyl-2-(10-methoxycarbonyldecyl)-4,4-dimethyl-3-oxazolidinyloxyl revealed that the penetration of ALA or LA into the liposomal membrane causes an increase in the membrane fluidity and a decrease in the phase-transition temperature of the lipid membrane. When human colon cancer cells (RPMI4788 and BM314) and normal mouse fibroblast (L-cell) were incubated with ALA, the membrane fluidity of the cancer cells significantly increased over that of normal cells. ALA made the cancer cell membrane more fluid than did LA. When ALA was administered at a concentration of 40 μg ml−1, it showed a strong cytotoxicity against the cancer cells, but not to the normal cells. On the other hand, LA (up to 80 μg ml−1) rather promoted growth of the cancer cells. These results seem able to be interpreted as an aspect of the selective cytotoxicities of ALA.